T-type calcium channels are known for regulating neuronal and cardiac pacemaker activity. They open in response to small membrane depolarizations that in turn trigger the initiation of action potentials[1]. Disruption of this sensitive signaling mechanism often leads to hyperexcitability disorders such as arrhythmia, epilepsy and pain[2-8]. Similarly, up-regulation of T-type channels in primary afferent fibers has been linked to chronic pain disorders, whereas ablation of these channels mediates analgesia[3, 4, 7]. The development of new selective T-type channel antagonists has not been a trivial undertaking, with only a few such small organic molecules having recently been identified[5].
Therefore, there is a continuing need for compounds that can modulate T-type calcium channels.